Rational drug design tools for the discovery of novel microbial natural products with applications in cosmetics

Cosmetics products can act based on their physicochemical properties (UV filters, colorants, etc.) or by binding to a specific receptor (tyrosinase, elastase etc). Since biology has augmented the number of known human skin's proteins, those proteins can be handled as drugable targets. Using common Rational Drug Design Tools such as Similarity Search, In Silico Screening and Prediction Models we can rationalize the bioprospection of natural sources producing appropriate metabolites for cosmetic use.

In the frame of the EU project “MICROSMETICS”, we exploit the microbial global biodiversity to discover and develop novel cosmeceutical agents. Starting from the CosIng Repository, accurate functional prediction model was created for all known cosmetic functions. Next the homology models of specific cosmetic target receptors were constructed (tyrosinase, elastase, hyluronidase and collagenase) for which the appropriate in vitro tests have already been developed. About 40.000 known microbial metabolites were processed through a consensus scoring prediction protocol using: a) functional prediction model b) virtual screening procedure for the selected receptors c) similarity search based on all known molecules from literature that bind to those receptors and d) toxicological profile filtering. From virtual screening, 93 metabolites ranked on the first 10% on all receptors, 125 on 3 receptors and 197 on 2 receptors. From similarity search 93 metabolites ranked on the top 10% for 3 targets (hyaluronidase lacks of known binders), 242 for 2 targets and 470 for 1 target. Combining those results, we selected 100 microorgnanisms that can produce those metabolites or analogues. They are cultivated, extracted and tested in vitro in order to be prioritized for the isolation and identification of possible novel cosmeuceutical agents.

Acknowledgment: This work has been financially supported by EU under the frame of MICROSMETICS project (FP7-PEOPLE-IAPP 2013, Grant agreement: 612276).